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Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.


ABSTRACT: Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent P. falciparum infections, and was associated with a lower risk of clinical episodes of malaria. Nine of the 14 vaccine candidates tested induced Ab-NK, including some less well-characterized antigens: P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role of Ab-NK activity in immunity against malaria and provide a potential mechanism for evaluating vaccine candidates.

SUBMITTER: Odera DO 

PROVIDER: S-EPMC7616656 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.

Odera Dennis O DO   Tuju James J   Mwai Kennedy K   Nkumama Irene N IN   Fürle Kristin K   Chege Timothy T   Kimathi Rinter R   Diehl Stefan S   Musasia Fauzia K FK   Rosenkranz Micha M   Njuguna Patricia P   Hamaluba Mainga M   Kapulu Melissa C MC   Frank Roland R   Osier Faith H A FHA   Abdi Abdirahman I AI   Chi Primus Che PC   de Laurent Zaydah Z   Jao Irene I   Kamuya Dorcas D   Kamuyu Gathoni G   Makale Johnstone J   Murungi Linda L   Musyoki Jennifer J   Muthui Michelle M   Mwacharo Jedidah J   Kariuki Silvia S   Mwanga Daniel D   Mwongeli Joyce J   Ndungu Francis F   Njue Maureen M   Nyangweso George G   Kimani Domitila D   Ngoi Joyce M JM   Musembi Janet J   Ngoto Omar O   Otieno Edward E   Ooko Michael M   Shangala Jimmy J   Wambua Juliana J   Mohammed Khadija Said KS   Omuoyo Donwilliams D   Mosobo Moses M   Kibinge Nelson N   Kinyanjui Sam S   Bejon Philip P   Lowe Brett B   Marsh Kevin K   Marsh Vicki V   Abebe Yonas Y   Billingsley Peter F PF   Sim Betty Kim Lee BKL   Hoffman Stephen L SL   James Eric R ER   Richie Thomas L TL   Audi Agnes A   Olewe Fredrick F   Oloo James J   Ongecha John J   Ongas Martin O MO   Koskei Nelly N   Bull Peter C PC   Hodgson Susanne H SH   Kivisi Cheryl C   Imwong Mallika M   Murphy Sean C SC   Ogutu Bernhards B   Tarning Joel J   Winterberg Markus M   Williams Thomas N TN  

Science translational medicine 20230208 682


Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized <i>Plasmodium falciparum</i> merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes. Ab-NK was associated with the successful control of parasitemia after experimental  ...[more]

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